Electrolytic reduction of polyhaloquinoline and polyhaloisoquinoline

ABSTRACT

HEPTACHLORO AND HEPTAFLUOROQUINOLINE AND ISOQUINOLINE ARE SELECTIVELY DEHALOGENATED BY ELECTROLYTIC REDUCTION.

United States Patent 3,687,826 ELECTROLYTIC REDUCTION OF POLYHALO- QUINOLINE AND POLYHALOISOQUINOLINE James N. Seiber, Davis, Calif., assignor to The Dow Chemical Company, Midland, Mich. No Drawing. Filed Jan. 25, 1971, Ser. No. 109,633 Int. Cl. C07b 29/06; C07d 33/36, 35/26 US. Cl. 204-73 R 7 Claims ABSTRACT OF THE DISCLOSURE Heptachloro and heptafluoroquinoline and isoquinoline are selectively dehalogenated by electrolytic reductlon.

BACKGROUND OF THE INVENTION Perchloroquinoline and perfiuoroquinoline can be prepared by vapor phase halogenation as described by Taplin in U.S. 3,420,883 or as described by British Patents 1,151,862 or 1,155,965.

The dehalogenation of haloaromatics by electrolytic reduction is generally known. The application of such techniques to a particular polyhalogenated compound to obtain a predictable product, however, is not known because there are many places where electrolytic reduction could occur. 1

SUMMARY OF THE INVENTION It has now been found according to the present invention that the electrolytic reduction of heptachloroquinoline, heptafiuoroquinoline, heptachloroisoquinoline, heptafluoroisoquinoline or any of these compounds containing an inert substituent gives a selective dehalogenation. This process gives desirable compounds having biological activity as fungicides for fungi, such as rice blast.

The quinoline compounds subject to electrolysis in the invention are perchloroquinoline, perfluoroquinoline or either of these compounds containing a substituent which is inert under the electrolysis conditions. The electrolysis selectively removes the halogen from the 4 position and then from the two position. The inert substituents are substituted in any positions on the rings except for the 4 position when one chlorine is removed and in the 2 and 4 positions when 2 halogens are removed. Representative examples of inert substituents include alkyl, cyano, amino, lower alkylamino and alkoxy. Compounds with these substituents include: 3methylhexachloroquinoline, 3- cyanohexachloroquinoline, 2 dimethylaminohexafiuoroquinoline and 5methoxyhexachloroquinoline. Preferred in the invention is the reduction of perchloroquinoline and perfiuoroquinoline, with the reduction of perchloroquinoline being especially preferred because of the demonstrated ease of reaction.

The isoquinoline compounds reduced in the invention are perchloroisoquinoline, perfluoroisoquinoline or either of these compounds containing an inert substituent. In the electrolysis, the halogen is selectively removed from the 1 position and then from the 4 position. The inert substituents are the same as those for quinoline and must be substituted in positions that do not interfere with the electrolytic reduction. Reduction of perchloroisoquinoline is preferred.

The desired electrolytic reduction of the invention is carried out by techniques that are generally known. These techniques are described below and exemplified in the specific embodiments. Broadly, the starting halogenated quinoline or isoquinoline is dissolved in a suitable solvent containing an electrolyte, the solution is added to an electrolysis cell and current is passed through the cell until the desired degree of reduction is obtained.

The concentration of the reactants in the electrolytic 3,687,826 Patented Aug. 29, 1972 cell may vary widely as different reactants and solvents are employed in the reaction. Reactant concentrations can be as high as their solubility will permit at the reaction temperature, with nearly saturated solutions being especially preferred.

The design of the electrolysis cell used in the present invention is not critical. Numerous electrolytic cells known in the art may be readily employed in the present invention. Preferred electrolytic cells have cathodes of mercury or lead. The anode may be essentially any chemically inert material with graphite and platinum being especially preferred. Such preferred cell may be arranged in any conventional design.

The electrolyte used in the present invention may vary widely. Preferred electrolytes in the present invention are neutral or acidic salts. The use of salts of strong bases may be detrimental to the progress of the reaction because of the tendency of such electrolytes to enter into reactions with the halogens. Specific examples of preferred electrolytes include sodium p-toluenesulfonate, sodium acetate, ammonium p-toluenesulfonate, ammonium chloride, ammonium fluoride, tetramethylammonium chloride, and hydrochloric acid, sulfuric acid, acetic acid or phosphoric acid used alone or in combination with ammonia or a tertiary amine. Especially preferred is the use of ammonium acetate, H acetic acid or I-ICl as the electrolyte. The concentration of the electrolyte may vary widely as different reactant concentrations, electrolytes, current densities and cathode potentials are employed.

The solvent employed in the electrolysis solution may vary widely as different reactants are employed in the electrolytic deh-alogenation. The solvent should dissolve all or most of the starting material and the electrolyte and should be inert or at least not detrimentally reactive under the electrolysis conditions. Solvents preferred in the present invention include the lower alcohols, lower alkylene glycol monoalkyl and lower amides. Representative examples of these preferred solvents include: alcohols such as methanol, ethanol, isopropanol and isobutyl alcohol; lower alkylene glycol monoalkyl and dialkyl ethers such as Z-methoxypropanol, ethoxyethanol, dime thoxyethane and 1,2-dimethoxypropane; and lower amides such as dimethylformamide and acetamide. These solvents of the present invention may be used either alone or in such combinations that a conducting medium results. Preferred cell fluids contain up to about 30% by by weight of water to assure proper solubility of the electrolyte.

In the operation of the electrolysis cell, the cathode potential is usually maintained greater (in terms of absolute value) than 0.5 'volt versus the standard calomel electrode, with cathode potentials of l.0 to 2.2 volts being especially preferred. The applied voltage provided by the power source may vary widely depending upon the IR drop of the reaction medium. The IR drop is preferably minimized to prevent overheating of the reaction cell.

The current density may preferably range from about 0.01-5 or more amp/in. of electrode with 0.1 to 1.0 amp/in. being especially preferred. At higher current densities, the selectivity of the reaction decreases; therefore, the current density should be adjusted to give the desired minimization of by-products.

The temperature of the electrolysis reaction may wary widely. The temperatures may be varied to maintain the cell contents as a liquid phase with temperatures from about 0 to about C. or more being preferred and temperatures of about 20 to about 80 C. being especially preferred.

The reduction is usually and most conveniently carried to less than 100% conversion to minimize the overreduction of the product under the reaction conditions. As a general rule, 70 to 95%- of the reduction theoretically required gives the most favorable yields of the desired product with minimum by-product. After the electrolysis, the product may be isolated by any conventional method.

The products produced by the electrolytic reduction are useful fungicides, especially for rice blast and tomato late blight.

SPECIFIC EMBODIMENTS Example 1.-Reduction of heptachloroquinoline An electrolytic cell was constructed in a 400 m1. beaker. The cathode was a pool of mercury in the bottom of the beaker having a surface area of about 4 sq. in., the anode was a platinum plate enclosed in a glass cup with a fritted bottom and the electrodes were connected to a constant voltage power source. The cell was also equipped with a saturated calomel reference electrode. A solution of 7 g. of heptachloroquinoline in 100 ml. of 1,2-dimethoxyethane, 75 ml. of methanol and ml. of 30% aqueous H 80 was added to the cell. The electrolysis was run between 58 and 65 C., the applied voltage was -30 volts, the cathode potential vs. the calomel electrode measured --0.64 to 0.75 volts and the current ranged between 1.2 and 1.5 amps. except that it was at 0.8 amps for a short period. The progress of the electrolysis was followed by periodic sampling of the cell fluid and the product isolated by solvent removal was analyzed by vapor phase chromatography (VPC) and mass spectroscopy. The results are shown in Table I.

TABLE I Electrolytic reduction of heptachloroquinoline Chloroquiuoline, percent VPC Example 2.Reduction of heptachloroquinoline An electrolysis cell was constructed in a rectangular polyethylene case equipped with a reflux condenser, calomel electrode, sample port and gas sparger for nitrogen. The cathode consisted of a vertical copper plate over which a flow of mercury was maintained during operation and two graphite anodes were placed on each side parallel to the cathode. The electrodes had a surface area of about 60 sq. in. and were placed about 1 cm. apart. Power for the cell was supplied by a potentiostat rated to deliver 40 volts and 30 amps.

In this electrolysis cell was placed a solution of 20 g. of heptachloroquinoline in 600 ml. of 1,2-dimethoxyethane, 500 ml. of methanol and 110 ml. of 30% aqueous H SO The cell was operated between 45 and 63 C. at an applied voltage of 3.8 volts initially and then after 10 minutes from 5.5 to 6.0 volts. The current ranged from 4.2 amps at the beginning to between 10.5 and 14.0 amps after 10 minutes while the cathode potential was 1.4 at the beginning and 2 to -2.2 volts thereafter. Mixing was obtained by sparging nitrogen into the liquid. Periodic samples of the cell fluid were removed, stripped of solvent and analyzed. The results of the electrolysis are shown in Table II.

TABLE II Electroly tie reduction of heptachloroquinoline Chloroquinoline, percent VPC Example 3.-Reduction of heptachloroquinoline using an ammonium acetate electrolyte In the cell of Example 2, a solution consisting of 20 g. of heptachloroquinoline, 600 ml. of 1,2-dimethoxyethane, 500 ml. of methanol, 75 g. of ammonium acetate and ml. of H 0 was electrolyzed. The temperature ranged from 55 to 62 C., the applied voltage ranged from 2.5 to 3.0 volts, the cathode potential ranged from 1.3 to -l.55 volts and the current ranged from 1.8 to 2.7 amps. After 16 minutes, the electrolysis was stopped, an additional 25 g. of ammonium acetate in 10 ml. of water was added and the reaction was resumed. Periodic samples were analyzed. The results are shown in Table III.

TABLE III In the electrolysis cell of Example 1, a solution consisting of 5.0 g. of heptachloroisoquinoline, 70 ml. of 1,2- dimethoxyethane, 60 ml. of methanol and 7.5 g. of ammonium acetate in 10 ml. of H 0 was electrolyzed. During the electrolysis, two 5.0 g. portions of heptachloroisoquinoline were added to the electrolysis cell one at 30 and the other at 70 minutes. The electrolysis was conducted between 49 and 58 C., the applied voltage was 11-14 volts, the cathode potential was -1.5 to -2.0 volts and the current was 0.40 to 0.56 amps. The analysis of cell fluid samples taken at the times indicated (before further reactant addition) are shown in Table IV.

TABLE IV Reduction of heptachloroisoquinoline Chloroisoquinoline, percent VPG Sample time, 3,4,5,6,7,8- 1,3,5,6,7,8- 3,5,6,7,8 nun. Hep hexa hexa penta In the same manner as shown by the examples above, heptafluoroquinoline may be electrolytically reduced to selectively replace the fluorine in the 4 position with hydrogen and then selectively replace the fluorine in the 2 position. Also in the same manner heptaifluoroisoquinoline can be selectively reduced to obtain a predominant monodehalogenated compound of 3,4,5,6,7,8-hexa fluoroisoquinoline and this compound can be further electrolytically reduced to remove the fluorine in the 4 position.

I claim:

1. An electrolytic process for selectively removing halogen from the 4 position when present and then optionally from the 2 position in a halogenated quinoline and from the 1 position when present and then optionally from the 4 position in a halogenated isoquinoline selected from the group consisting of heptahaloquinoline, heptahaloisoquinoline, a hexahaloquinoline, and a hexahaloisoquino- 5. The process of claim 1 wherein the isoquinolines line, said hexahalo compounds having no other substituent are selectively reduced. which is reactive in the process wherein halogen is fluorine The Process of Clalm 5 wherein heptachlofolsoquln' or chlorine which comprises applying to the cathode an oline is reducedelectrical potential of 0.5 to 2.2 volts measured 5 The PICK;ess 0f Clalm 5 Whefelll against a saturated calomel electrode and a current density chloroisoqumoline is reduced of about 0.01 to about 5 amperes/sq. in. of cathode sur- References Cited ifiicilZZ1$I2$SEZZEZ fififii iicifiiii UNITED STATES PATENTS 2. The process of claim 1 wherein the quinolines are 10 ga gs F E selectively reduced. g

3. The process of claim 2 wherein heptachloroquinoline F EIGN PATENTS is reduced. 762,873 5/1951 Canada 20472 4. The process of claim 2 wherein 2,3,5,6,7,8-hexa- I J ch10) quinoline is reduced. 15 FREDERICK C. EDMUNDSON, Prrmary Examiner 

